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Current Developments in Hepatitis C

05 May 2017Essay Samples

Introduction

Prince and colleagues as post-transfusion non-A, non-B hepatitis first described hepatitis C in 1974. Consequently, chronicity of post-transfusion non-A, non-B hepatitis was discovered as a blandly symptomatic disease with elevation of the liver enzyme alanine aminotransferase (ALT) and chronic hepatitis seen on liver biopsy. The infectious nature of the entity was confirmed when the disease could be conveyed from humans to chimpanzees. The etiologic agent, the hepatitis C virus (HCV), was recognized as a genetic sequence in 1989 by Choo through random polymerase chain reaction (PCR) assays in plasma of chimpanzees chronically infected with non-A, non-B hepatitis, that led to the development of a first-generation HCV antibody test that identified HCV as the basis of majority cases of formerly "diagnosed" non-A, non-B hepatitis.

Current Treatment and Developments

Treatment against chronic hepatitis C includes interferon alfa alone or in combination with ribavirin. Interferon alfa has antiviral and immunomodulatory movement. The antiviral effects are chiefly arbitrated by way of increase in intracellular 2'5' oligoadenylate synthetase and protein kinase enzymes, which restrain creation of viral compounds. Interferon also influences the immune system by way of various mechanisms, for instance an increased expression of HLA class I antigens on hepatocyte cell membranes and the promotion of natural killer cell activity, that simultaneously lead to the increased clearance of HCV-infected hepatocytes. The way of action of ribavirin in fusion with interferon is inadequately learned, but it may involve antiviral activity via chain termination of HCV-specific RNA-dependent RNA-polymerase or act as an immune modulator by changing the anti-HCV immune response from a T helper 2 cell- dominated response with humoral activity to a T helper 1 cell- -dominated response, with predominantly cytotoxic activity (Lau, pp 1002-1009)

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The greatest results in adults are currently obtained with an admixture of-interferon plus ribavirin, for 6 or 12 months. Sustained response can be achieved after 6 months of combined therapy in 65-70% of patients with genotype 2 or 3. In patients with genotype 1 and 4, and a high viral load (more than 2 million copies/ml), sustained replication is only 30-40% after12 months of treatment, barely better if the viral load is low. The premonitory conditions for good response are age < 40 years, female, genotype non-1, viral load, absence of cirrhosis (Davis, pp 104-114).

The side effects of interferon are fever, fatigue, depression, weight loss, thrombopenia, neutropenia, and hypothyroidism. Ribavirin may cause anemia. Currently, promising results in adults have been published with pegylated interferon that allows one-time weekly injections, with development of the response rate as compared with interferon, and better tolerance (Zeuzem, 2000). There is a momentum to using a combination of Peg interferon and ribavirin. In children, studies are finite, comprise small numbers of patients, and use a monotherapy with interferon. The success rate varies from 8 to 56%, with a mean at 40% that is better than the altogether response rate to monotherapy in adults (15-30%). The sequence is too small to estimate the role of genotype or mode of contamination. None has been recognized using a combination with ribavirin.

Vaccination against HCV is so far not obtainable, notwithstanding intense efforts. The larger problems are the high rate of mutation of HCV (quasi-species), with the hypervariable region being the site of a principal neutralization epitope, the delayed emanation of neutralizing antibodies, the problems of establishing a favorable tissue culture, and conditions of animal studies in chimpanzee. Powerful cellular immune response is implicated in viral clearance. The present developments include DNA-based vaccination 20, chimeric viruses expressing HCV genes 21, or viruslike particles.

The time of treatment for chronic hepatitis C with interferon and ribavirin is 48 weeks in genotype 1 patients and 24 weeks in genotype 2 and 3 patients. Treatment result is measured in terms of HCV viral load, and a treatment response is described as deprivation of perceptible plasma HCV RNA (< 50 IU/mL or < 100 copies/mL). An SVR is defined as undetectable HCV RNA 6 months after the end of treatment.
There are three different outcomes of therapy:

1. End-of-treatment response, which is sustained through post treatment month 6 (SVR)
2. End-of-treatment response with reversion of HCV viremia after treatment is ceased, generally within first 12 weeks (response-relapse)
3. HCV RNA still perceptible at the end of treatment and generally correspondingly during treatment (non-response).

But once an SVR has been concluded at 6 months after treatment, the patient can be contemplated cured of chronic hepatitis C. Studies have shown that 6 years subsequent to an SVR following interferon monotherapy, viral relapse occurred in 10% to 28% of patients, even though these relapse patients protracted to have usual ALT levels and showed minimum inflammation and no fibrosis on liver biopsy. Also, none of the SVR patients developed cirrhosis, liver decompensation, or HCC contrasted with a 30% rate of such intricacy in non-responders. Liver-related death rate after an average of 6 years was 0% in patients with a sustained response contrasted with 2.2% in non-responders.

By the overture of interferon plus ribavirin fusion therapy, viral relapse following an SVR has become rare. Viral relapse occurred in 0.8% of patients at post treatment year 1 and in 1.8% at year 2. At post treatment year 4, there was no more viral relapse. (McHutchison, pp 24-34) Succeeding an SVR infra any treatment, notable improvement of inflammation and retraction of fibrosis are observed, and even the retraction of cirrhosis has been reported in 49% of patients after successful treatment. (Poynard, pp 1303-131)

An SVR is the best consequence of HCV therapy. Nonetheless, there are still advantages of interferon-based HCV therapy, indeed when the virus is not forever cleaned. Liver inflammation ameliorates, and the rate of fibrosis progression is slowed (Alri et. al, 2001 and Shiratori et. al, 2000). In a study by Shiratori and colleagues fibrosis advancement utilizing the METAVIR fibrosis score (0-4) was collated betwixt:

 HCV patients who had a sustained response
 Patients who had treatment but had no viral response
 Patients who did not had any treatment.

Subsequently, after more than 3 years of follow-up, fibrosis change was -0.88 in the SVR group, +0.15 in the nonresponse group, and +0.59 in the no treatment group. Clinically, when collated with no treatment, interferon-based monotherapy in content HCV-related cirrhosis, that are majorly without viral clearance, has been analogous with a reduced rate of progression to decompensation or HCC and reduced mortality (Nishiguchi, pp 196-97)

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